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Network - Spring 2012


Drug starves fat cells in obese monkeys: Next up, first clinical trial for obese prostate cancer patients

Obese rhesus monkeys treated with an experimental drug that starves fat cells by destroying their blood supply lost, on average, 11% of their body weight in four weeks.

Treatment also slimmed the monkeys’ waistlines, reduced their body mass index (BMI) and decreased body fat. All measurements were unchanged in untreated monkeys.

“Development of this compound for human use could provide a non-surgical way to actually reduce accumulated fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat,” says co-senior author Renata Pasqualini, Ph.D., professor in MD Anderson’s David H. Koch Center for Applied Research of Genitourinary Cancers.

Most drugs developed to treat obesity focus on suppressing appetite or increasing metabolism, but both approaches have been thwarted by toxic side effects.
The MD Anderson group designed a new drug, Adipotide™. It includes a homing component that binds to a protein on the surface of fat-supporting blood vessels and a synthetic peptide that triggers cell death. With their blood supply gone, fat cells die and metabolize.

Obesity is a major risk factor for developing cancer, and obese patients tend to do worse in surgery, with radiation and on chemotherapy, says co-senior author Wadih Arap, M.D., Ph.D., professor in the Koch Center.

The researchers are preparing a clinical trial in which obese prostate cancer patients would receive daily injections of Adipotide for 28 days. “The question is: Will their prostate cancer be affected if we can reduce their body weight and the associated health risks?” Arap says.

Prognostic model for patients with cancer therapy-induced MDS

A large-scale analysis of patients whose myelodysplastic syndrome (MDS) is related to earlier cancer treatment overturns the notion that all of them have a poor prognosis.

MDS is characterized by a deficiency in the number of blood cells caused by bone marrow that's not functioning correctly.

“MDS patients whose disease springs from earlier radiation, chemotherapy or both treatments are usually told that they have a poor prognosis. But by analyzing survival risk factors in a large patient population, we’ve found these patients fall into good, intermediate and poor prognostic groups,” says study leader Guillermo Garcia-Manero, M.D., professor in the Department of Leukemia.

Understanding their differences will better guide treatment decisions for these patients, he says.

The research team analyzed 1,950 MD Anderson patients treated between 1998 and 2007. It found 438 had been treated for cancer before their MDS diagnosis. Of these, 279 patients who had received chemotherapy, radiation therapy or both were analyzed.

A first round of analysis identified at least 15 factors associated with overall survival when considered as isolated, single variables. Next, the researchers conducted a multi-variable analysis that narrowed factors, reducing those that affect overall survival to seven.

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